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NEW ADVANCES IN THE
BASIC AND CLINICAL
GASTROENTEROLOGY
Edited by Tomasz Brzozowski
NEW ADVANCES IN THE
BASIC AND CLINICAL
GASTROENTEROLOGY
Edited by Tomasz Brzozowski
New Advances in the Basic and Clinical Gastroenterology
Edited by Tomasz Brzozowski
Published by InTech
Janeza Trdine 9, 51000 Rijeka, Croatia
Copyright © 2012 InTech
All chapters are Open Access distributed under the Creative Commons Attribution 3.0
license, which allows users to download, copy and build upon published articles even for
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As for readers, this license allows users to download, copy and build upon published
chapters even for commercial purposes, as long as the author and publisher are properly
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Notice
Statements and opinions expressed in the chapters are these of the individual contributors
and not necessarily those of the editors or publisher. No responsibility is accepted for the
accuracy of information contained in the published chapters. The publisher assumes no
responsibility for any damage or injury to persons or property arising out of the use of any
materials, instructions, methods or ideas contained in the book.
Publishing Process Manager Vana Persen
Technical Editor Teodora Smiljanic
Cover Designer InTech Design Team
First published April, 2012
Printed in Croatia
A free online edition of this book is available at www.intechopen.com
Additional hard copies can be obtained from [email protected]
New Advances in the Basic and Clinical Gastroenterology, Edited by Tomasz Brzozowski
p. cm.
ISBN 978-953-51-0521-3
Contents
Section 1 Emerging Impact of Probiotics in Gastroenterology 1
Chapter 1 Intestinal Microbial Flora –
Effect of Probiotics in Newborns 3
Pasqua Betta and Giovanna Vitaliti
Chapter 2 Probiotics – What They Are,
Their Benefits and Challenges 21
M.S. Thantsha, C.I. Mamvura and J. Booyens
Chapter 3 The Impact of Probiotics
on the Gastrointestinal Physiology 51
Erdal Matur and Evren Eraslan
Chapter 4 The Benefits of Probiotics in
Human and Animal Nutrition 75
Camila Boaventura, Rafael Azevedo,
Ana Uetanabaro, Jacques Nicoli
and Luis Gustavo Braga
Chapter 5 Gut Microbiota in Disease Diagnostics 101
Knut Rudi and Morten Isaksen
Chapter 6 Delivery of Probiotic Microorganisms
into Gastrointestinal Tract by Food Products 121
Amir Mohammad Mortazavian,
Reza Mohammadi and Sara Sohrabvandi
Section 2 Pathomechanism and Management
of the Upper Gastrointestinal Tract Disorders 147
Chapter 7 Chronic NSAIDs Therapy and Upper
Gastrointestinal Tract – Mechanism of
Injury, Mucosal Defense, Risk Factors for
Complication Development and Clinical Management 149
Francesco Azzaroli, Andrea Lisotti, Claudio Calvanese,
Laura Turco and Giuseppe Mazzella
VI Contents
Chapter 8 Swallowing Disorders
Related to Vertebrogenic Dysfunctions 175
Eva Vanaskova, Jiri Dolina and Ales Hep
Chapter 9 Enhanced Ulcer Recognition from
Capsule Endoscopic Images Using Texture Analysis 185
Vasileios Charisis, Leontios Hadjileontiadis and George Sergiadis
Chapter 10 Methods of Protein Digestive
Stability Assay – State of the Art 211
Mikhail Akimov and Vladimir Bezuglov
Chapter 11 Mesenteric Vascular Disease 235
Amer Jomha and Markus Schmidt
Chapter 12 A Case Based Approach to
Severe Microcytic Anemia in Children 247
Andrew S. Freiberg
Section 3 Pathophysiology and Treatment of
Pancreatic and Intestinal Disorders 267
Chapter 13 Emerging Approaches for the
Treatment of Fat Malabsorption
Due to Exocrine Pancreatic Insufficiency 269
Saoussen Turki and Héla Kallel
Chapter 14 Pharmacology of Traditional Herbal
Medicines and Their Active Principles
Used in the Treatment of Peptic Ulcer,
Diarrhoea and Inflammatory Bowel Disease 297
Bhavani Prasad Kota, Aik Wei Teoh and Basil D. Roufogalis
Chapter 15 Evaluating Lymphoma Risk in
Inflammatory Bowel Disease 311
Neeraj Prasad
Chapter 16 Development, Optimization and
Absorption Mechanism of DHP107, Oral Paclitaxel
Formulation for Single-Agent Anticancer Therapy 357
In-Hyun Lee, Jung Wan Hong, Yura Jang,
Yeong Taek Park and Hesson Chung
Chapter 17 Differences in the Development of the Small Intestine
Between Gnotobiotic and Conventionally Bred Piglets 375
Soňa Gancarčíková
Chapter 18 Superior Mesenteric Artery Syndrome 415
Rani Sophia and Waseem Ahmad Bashir
Contents VII
Chapter 19 Appendiceal MALT Lymphoma in
Childhood – Presentation and Evolution 419
Antonio Marte, Gianpaolo Marte,
Lucia Pintozzi and Pio Parmeggiani
Chapter 20 The Surgical Management of Chronic Pancreatitis 429
S. Burmeister, P.C. Bornman, J.E.J. Krige and S.R. Thomson
Chapter 21 The Influence of Colonic Irrigation
on Human Intestinal Microbiota 449
Yoko Uchiyama-Tanaka
Section 4 Diseases of the Liver and Biliary Tract 459
Chapter 22 Pancreato-Biliary Cancers –
Diagnosis and Management 461
Nam Q. Nguyen
Chapter 23 Recontructive Biliary Surgery in the
Treatment of Iatrogenic Bile Duct Injuries 477
Beata Jabłońska and Paweł Lampe
Chapter 24 Hepatic Encephalopathy 495
Om Parkash, Adil Aub and Saeed Hamid
Chapter 25 Adverse Reactions and Gastrointestinal Tract 511
A. Lorenzo Hernández, E. Ramirez
and Jf. Sánchez Muñoz-Torrero
Chapter 26 Selected Algorithms of Computational
Intelligence in Gastric Cancer Decision Making 529
Elisabeth Rakus-Andersson
Section 1
Emerging Impact of
Probiotics in Gastroenterology
1
Intestinal Microbial Flora –
Effect of Probiotics in Newborns
Pasqua Betta* and Giovanna Vitaliti
U.O UTIN, Department of Pediatrics,
University of Catania
Italy
1. Introduction
The surface of the human gut has a surplus area of 200-250 m2 in order to contain, between
intraepithelial lymphocytes and lamina propria, Peyer’s patches and lymphoid follicles, the
lymphoid tissue, while hosts a flora of about 800 different bacteria species with over 7000
strains. The 99% are obligate anaerobes and varies species were then classified using
traditional anaerobic culture techniques. More than 50% of the dominant gut microbiota
(corresponding to 10 8-10 11 per gram of faeces) cannot be identified using traditional colture
,but molecular approaches, based on the use of 165 ribosomal DNA molecular (Mai &
Morris, 2004). Most of these bacteria colonizes the large intestine (in a range of 10-12
bacteria/g). The bacterial count of the small intestine (duodedum and jejunum) is
considerably lower (approximately 104-7 bacteria/ml) than Streptococcus Lactobacillus,
Enterobacteriaceae corresponding to the transient microbiota.
The main bacterial species represented in the human large intestine (colon) are distributed
with densities higher than 10 9-11 per gram of contents, and these high densities can be
explained by the slow transit and low redox potential . In this intestinal tract we can mostly
find bifidobacteria and bacteroides ,bifidobacterium clostridium. The fecal microbiota
contains 10 9 _10 11 CFU per gram, and microorganism in about 40% of their weight. The
dominant microbiota is represented by strict anaerobes , while the sub-dominant microbiota
by facultative anaerobes. In addition to the resident microbiota (dominant and sub
dominant), the faeces contain the transient microbiota, that is extremely variable, including
Enterobacteriacee (Citrobacter, Klebsiella, Proteus ) and Enterobacter (Pseudomonas) and
yeast ( Candida) CFU per gram (Table 1) (Zoetendal et al, 2004).
2. Intestinal microbiota in newborn
The normal human microflora is a complex ecosystem that somehow depends on enteric
nutrients for establishing colonization. At birth ,the digestive tract is sterile. This balance of
the intestinal microflora is similar to that of adult from about two years of age (Hammerman
et al, 2004).
*
Corresponding Author
4 New Advances in the Basic and Clinical Gastroenterology
Mouth 200 species
Stomach,duodenum pH 2,5-3,5 destructive to most of
bacteria 101_103 unit /ml
Lactobacillus,Streptococcus,
Jejunum,ileum 10 4_ 10 6 unit /ml bifidobacteria and
bacteroides ,bifidobacterium
clostridium
Aerobes
Colon 300-400 several species 1010_ 1011 unit
/ml
Enterobacteriacee (Citrobacter,
Klebsiella,Proteus)o(Pseudomonas)
Candida.
Anaerobes
Table 1. Composition and topographical features of intestinal microbiota
Diet and environmental conditions can influence this ecosystem. At birth intestinal
colonization derives from microorganism of the vaginal mucoses of the mother and faecal
microflora . The microbial imprinting depends on the mode and location of delivery.
Literature data shows that infants born in a hospital environment, by caesarean section, have a
high component of anaerobic microbial flora (Clostridia) and high post of Gram-negative
enterobacteria. Those born prematurely by vaginal delivery and breast-feed have a rather rich
in Lactobacilli and Bifidobacteria microflora. (Grönlund et al, 1999; Hall et al, 1990)
Diet can influence the microbiota, while breast-feeding promotes an intestine microbiota in
which Bifidobacteria predominate, while coliform, enterococci and bacteroides predominate
in formula bottle-fed baby.
Escherichia coli and Streptococcus are included among the first bacteria to colonize the
digestive tract. After them, strict anaerobes (Bacteroides, Bifidobacteri ,Clostridium)
establish during the first week of life, when the diet plays a fundamental role. (Mackie et al,
1999). The pattern of bacterial colonization in the premature neonatal gut is different from
the one of healthy, full term infant gut. Aberrant pre-term infants admitted to NICU, born
by caesarean section, are more often separated from their mother and kept in an aseptic
intensive care setting, treated with broad-spectrum antibiotics. This is the reason why they
show a highly modified bacterial flora, consisting of less than 20 species of bacteria, with a
predominance of Staphylococcus (aureus and coagulase negative) among aerobic microorganisms, and Enterobacteriaceae (Klebsiella), among enterococci and anaerobic Clostridia
(Dai et al, 1999; Gothefor, 1989).
It is believed that microbial diversity is an important factor in determining the stability of
the ecosystem and that the fecal loss of diversity predisposes the preterm gastrointestinal
colonization of antibiotic-resistant bacteria and fungi colonization with a consequent
potential risk of infection, thus contributing to the development of necrotizing enterocolitis
(NEC) (Fanaro et al, 2003; Sakata et al, 1985)
2.1 Structure and function of intestinal microbial flora
The intestinal microbial flora has numerous functions, even if the most of them has not yet
been identified. Among these functions, we can report its anatomical –functional role, its
Intestinal Microbial Flora – Effect of Probiotics in Newborns 5
protective function, in particular the “barrier effect”, referring to the physiological capacity
of the endogenous bacterial microflora to inhibit colonization of the intestine by pathogenic
microorganism. It is already known that the intestinal microbial flora influences food
digestion ,absorption and fermentation, the immune system response, peristalsis,
production of vitamins such as B-vitamins, influencing moreover the turnover of intestinal
epithelial cells. In addition the metabolism of gut microflora influences hormonal secretion.
Bacterial colonization of human gut by environmental microbes begins immediately after
birth; the composition of intestinal microbiota, relatively simple in infants, becomes more
complex with increasing in age, with a high degree of variability among human individuals.
It is believed that microbial diversity is an important factor in determining the stability of
the ecosystem and that fecal loss of diversity predisposes the preterm gastrointestinal
colonization of antibiotic-resistant bacteria and fungi with the consequent potential risk of
infection (Cummings & Macfarlane, 1991; Montalto et al, 2009; Neish, 2002).
2.2 Gut microflora and immunity
The mucosal membrane of the intestines, with an area of approximately 200 m2, is
constantly challenged by the enormous amount of antigens from food, from the intestinal
microbial flora and from inhaled particles that also reach the intestines. It is not surprising
therefore that approximately the eighty per cent of the immune system is found in the area
of the intestinal tract and it is particularly prevalent in the small intestine. The intestinal
immune system is referred as GALT (gut-associated-lymphoid tissue). It consists of Peyer’s
patches, which are units of lymphoid cells, single lymphocytes scattered in the lamina
propria and intraepithelial lymphocytes spread in the intestinal epithelia.
The immune system of infants is not fully developed. The structures of the mucosal immune
system are fully developed in utero by 28 weeks gestation, but in the absence of intrauterine
infections, activation does not occur until after birth. Maturation of the mucosal immune
system and establishment of protective immunity is usually fully developed in the first
years of life. In addition the exposure to pathogenic and commensal bacteria, the major
modifier of the development patterns in the neonatal period, depends on infant feeding
practices. (Brandtzaeg, 2001; Gleeson et al, 2004)
Bacterial colonisation of the intestine is important for the development of the immune
system. The intestine has an important function in working as a barrier.This barrier is
maintained by tight-junctions between the epithelial cells, by production of IgA antibodies
and by influencing the normal microbial flora. It is extremely important that only harmless
substances are absorbed while the harmful substances are secreted via the faeces.
Studies show that individuals allergic to cow´s milk have defective IgA production and an
increased permeability of the intestinal mucosa. This results in an increased absorption of
macromolecules by the intestinal mucosa. The increased permeability is most probably
caused by local inflammations due to immunological reactions against the allergen. This
damages the intestinal mucosa
2.3 Modification of the intestinal flora micro-ecosystem
During the past century our lifestyle has dramatically changed regarding hygienic
measures, diet, standards of living and usage of medical drugs. Today our diet largely
6 New Advances in the Basic and Clinical Gastroenterology
includes industrially produced sterilized food and the use of different kinds of
preservatives. This has led to a decreased intake of bacteria, particularly lactic acid
producing bacteria .
The widespread use of antibiotics in healthcare and agriculture, antibacterial substance is
also something new for human kind. We have in so many ways sterilized our environment,
which is detrimental to the microbial (Cummings & Macfarlane G.T., 1997; Vanderhoof &
Young, 1998).
3. What are probiotics?
The term ‘probiotic’ was proposed in 1965 to denote an organism or substance that
contributes to the intestinal microbial balance. The definition of probiotics has subsequently
evolved to emphasise a beneficial effect to health over effects on microbiota composition,
underscoring the requirement of rigorously proven clinical efficacy. Most probiotic bacterial
strains were originally isolated from the intestinal microbiota of healthy humans and the
probiotics most thoroughly investigated thus far belong to the genera lactobacilli and
bifidobacteria (Caramia G., 2004).
Probiotics have several effects, including modulating the gut microbiota, promoting
mucosal barrier functions, inhibiting mucosal pathogen adherence and interacting with the
innate and adaptive immune systems of the host, which may promote resistance against
pathogens. The intestinal microbiota constitutes an important aspect of the mucosal barrier
the function of which is to restrict mucosal colonisation by pathogens, to prevent pathogens
from penetrating the mucosa and to initiate and regulate immune responses
3.1 Proved beneficial effects on the host
Prerequisites for probiotics’ efficacy are human origin, resistance transit gastric capacity to
colonize survival in and adhesion, competitive exclusion of pathogens or harmful antigens
to specific areas of the gastrointestinal tract, vitality, verifiable and stability conservation,
production substances with antimicrobial action, exclusion of resistance transferable
antibiotic. No pathogenicity and / or toxicity has ever been demonstrated on the host.
3.2 Effect of probiotics
Among their effects, the most important are: competition to the more valid nutrients and
enteric epithelial anchorage sites; reduction of intestinal pH values for high production of
lactic acid from lactose and acetic acid from carbohydrates, which selects the growth of
lactobacilli; production of bacteriocins, peptides with bactericidal activity towards related
bacteria species; metabolism of certain nutrients in the volatile fatty acids; activation of
mucosal immunity, with increased synthesis of secretory IgA, and phagocytosis; stimulation
of production of various cytokines
3.3 Mechanism of action of probiotics
The functional interactions between bacteria, gut epithelium, gut mucosal immune system
and systemic immune system are the basis of the mechanisms of direct and indirect effects
of probiotics. The direct effect of probiotics in the lumen are: competition with pathogens for
Intestinal Microbial Flora – Effect of Probiotics in Newborns 7
nutrients, production of antimicrobial substances and in particular organic acids
competitive inhibition on the receptor sites, change in the composition of mucins hydrolysis
of toxins, receptorial hydrolisis, and nitric oxide (NO), while the indirect effect largely
depends on the site of interaction between the probiotic and the effectors of the immune
response, topographically located in the intestinal tract.
There is evidence, in vitro and in vivo, on effects of different probiotics on specific
mechanisms of the immune response. The starting point is the interaction between probiotic
and the host intestinal mucosa, but it seems clear that not all probiotics have the same initial
contact (immune cells, enterocytes, etc.).
There are several literature data that have demonstrated the interaction between probiotics
and the immune system, in particular it has been demonstrated their capacity to stimulate
the production of intestinal mucines, their trophic effect on intestinal epithelium, the reestablishment of the intestinal mucosa integrity, the stimulation of the IgA-mediated
immune response against viral pathogens. All these effects have been demonstrated in
experimental studies and in some clinical studies, even if it is not still clear the main
mechanism of action and it is conceivable that different mechanisms of action contribute to
the efficacy of probiotics, with a different role in different clinical situations (Vanderhoof &
Young, 1998).
3.4 Safety
The oral consumption of viable bacteria in infancy naturally raises safety concerns. Products
containing probiotics are widely available in many countries and, despite the growing use of
such products in recent years, no increase in Lactobacillus bacteraemia has been detected.
Nevertheless, the average yearly incidence of Lactobacillus bacteraemia in Finland between
the years 1995 and 2000 was 0.3 cases/100,000 inhabitants. Importantly, 11 out of the 48
isolated strains were identical to Lactobacillus GG, the most commonly used probiotic
strain. Lactobacillus bacteraemia is considered to be of clinical significance; immunesuppression, prior prolonged hospitalisation and surgical interventions have been identified
as predisposing factors. Nonetheless, clinical trials with products containing both
lactobacilli and bifidobacteria have demonstrated the safety of these probiotics in infants
and children, and in a recent study, the use of L. casei was found to be safe also in critically
ill children
In a trial assessing the safety of long-term consumption of infant formula containing B. lactis
and S. thermophilus, the supplemented formulas were demonstrated to be safe and well
tolerated. No serious adverse effects have been reported in the trials involving premature
neonates, but it should be noted that the studies were not primarily designed to assess their
safety (Hammerman et al, 2006)
4. Probiotics and gastrointestinal disorders
The presence of Bifidobacteria in artificial milk can contribute to the induction of a
significant increase of Bifidobacteria in the intestinal tract, promotes the development of a
protective microflora, similar to that one of the breast- fed newborn, contributes to the
modulation of immune-defenses, giving them a major efficiency (Langhendries et al, 1995;
Fukushima et al, 1998).